Interbody bone implant device

ABSTRACT

A composite interbody bone implant device is provided including a body having a non-bone composition, such as a polymer, formed into a shape and including one or more cavities. An osteoinductive material, such as bone allograft tissue, may be retained in the one or more cavities of the body. The body is formable via injection molding and/or machining into a shape and size adapted for implantation at a surgical site. The dimensions of the body include a length, a width and a thickness, and the thickness of the body may be less than at least one of the length and width.

BACKGROUND

The use of bone grafts and bone substitute materials in orthopedicmedicine is known. Conventionally, bone tissue regeneration is achievedby filling a bone repair site with a bone graft. Over time, the bonegraft is incorporated by the host and new bone remodels the bone graft.In order to place the bone graft, it is common to use a monolithic bonegraft or to form an osteoimplant comprising particulated bone in acarrier. The carrier is thus chosen to be biocompatible, to beresorbable, and to have release characteristics such that the bone graftis accessible. The natural cellular healing and remodeling mechanisms ofthe body coordinate removal of bone and bone grafts by osteoclast cellsand formation of bone by osteoblast cells.

In the spinal surgery field, surgical procedures are often performed tocorrect problems with displaced, damaged or degenerated intervertebraldiscs due to trauma, disease or aging. Bone graft materials are oftenused in spine fusion surgery. Current spinal fusion implants utilizegrafts of either bone or artificial implants to fill the intervertebraldisc space.

In particular, one method of treating a damaged disc is by immobilizingthe area around the injured portion and fusing the immobilized portionby promoting bone growth between the immobilized spine portions. Thisoften requires implantation of an intervertebral device to provide thedesired spacing between adjacent vertebrae to maintain foraminal heightand decompression. That is, an intervertebral implant comprising aninterbody fusion device may be inserted into the intervertebral discspace of two neighboring vertebral bodies or into the space created byremoval of damaged portions of the spine.

In some instances, a formed implant, whether monolithic or particulatedand in a carrier, is substantially solid at the time of implantation andthus does not conform to the implant site. Further, most implants aresubstantially formed at the time of implantation in limited sizes andshapes and provide little ability for customization.

While generally effective, the use of bone grafts has some limitations.Autologous bone grafts, being obtained from the patient, requireadditional surgery and present increased risks associated with itsharvesting, such as risk of infection, blood loss and compromisedstructural integrity at the donor site. Bone grafts using cortical boneremodel slowly because of their limited porosity. Traditional bonesubstitute materials and bone chips are more quickly remodeled butcannot immediately provide mechanical support. In addition, while bonesubstitute materials and bone chips can be used to fill oddly shapedbone defects, such materials are not as well suited for wrapping orresurfacing bone. Indeed, the use of bone grafts is generally limited bythe available shapes and sizes of grafts provided.

With regards to bone grafts, allograft bone is a reasonable bone graftsubstitute for autologous bone. It is readily available from cadaversand avoids the surgical complications and patient morbidity associatedwith harvesting autologous bone. Allograft bone is essentially aload-bearing matrix comprising cross-linked collagen, hydroxyapatite,and osteoinductive bone morphogenetic proteins. Human allograft tissueis widely used in orthopaedic surgery.

Indeed, allograft is a preferred material by surgeons for conductinginterbody fusions because it will remodel over time into host bonewithin the fusion mass. However, though allograft tissue has certainadvantages over the other treatments, allograft is typically availablein only limited size ranges, thus making it difficult to provideimplants, in particular, interbody implants in a preferred geometricalshape. Indeed, allograft may only provide temporary support, as it isdifficult to manufacture the allograft with a consistent shape andstrength.

Accordingly, it would be desirable to construct an implant, particularlyan interbody implant, to better utilize the benefits of allografttreatment.

SUMMARY

The present disclosure fills the foregoing need by providing devices(e.g., medical devices), systems and methods for enhancing the utilityof allograft tissue as an interbody fusion material. In particular, thepresent disclosure provides an advantageous implant device comprising acomposite of allograft bone tissue and a non-bone composition such as apolymer composition, e.g., poly-ether-ether-ketone (PEEK) and/or otherpolymer compositions. According to some embodiments, a composite boneimplant device is provided which utilizes and retains allograft pieceswithin a polymer structure. This advantageously enables the beneficialproperties of allograft tissue and the beneficial attributes of polymersto be fully realized. For example, the remodeling capability ofallograft tissue is advantageously combined with the polymer's abilityto enable implants to be formed into any geometrical shape or size.

According to one aspect, a bone implant device is provided comprising abody, which comprises a non-bone composition formed into a shape andincluding at least one cavity; and a biocompatible material providedwithin said at least one cavity of the body, wherein the body isformable into a shape and size adapted for implantation at a surgicalsite.

According to another aspect, a composite interbody bone implant deviceis provided comprising a body, which comprises a non-bone compositionformed into a shape and including a plurality of cavities and anosteoinductive material provided within said cavities of the body,wherein the body is formable into a shape and size adapted forimplantation at a surgical site.

According to yet another aspect, a composite interbody bone implantdevice is provided comprising a body comprises a polymer formed into ashape and including a plurality of cavities, and an allograft materialprovided within said cavities of the body, wherein the body is formableinto a shape and size adapted for implantation at a surgical site.

While multiple embodiments are disclosed, still other embodiments of thepresent disclosure will become apparent to those skilled in the art fromthe following detailed description, which is to be read in connectionwith the accompanying drawing(s). As will be apparent, the disclosure iscapable of modifications in various obvious aspects, all withoutdeparting from the spirit and scope of the present disclosure.Accordingly, the detailed description is to be regarded as illustrativein nature and not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

In part, other aspects, features, benefits and advantages of theembodiments will be apparent with regard to the following description,appended claims and accompanying drawing(s) where:

FIG. 1 is a top view of an exemplary composite bone implant deviceaccording to one embodiment;

FIG. 2 is a front view of the device of FIG. 1;

FIGS. 3-4 are top views of exemplary composite interbody bone implantdevices for transforaminal lumbar interbody fusion (TLIF) according toalternate embodiments;

FIGS. 5, 7 and 8 are top views of exemplary composite interbody boneimplant devices for anterior lumbar interbody fusion (ALIF) according toalternate embodiments;

FIG. 6 is a side view of the device of FIG. 5;

FIG. 9 is a top view of an exemplary composite interbody bone implantdevice for anterior cervical discectomy and fusion (ACDF) according toan alternate embodiment;

FIG. 10 is an exemplary depiction of an implant device secured by aninsertion tool;

FIG. 11 depicts side and top views of an exemplary implant deviceinserted within an intervertebral disc space in a first position; and

FIG. 12 depicts side and top views of an exemplary implant deviceinserted within an intervertebral disc space and rotated to a secondposition.

DEFINITIONS

To aid in the understanding of the disclosure, the followingnon-limiting definitions are provided:

“Bioactive agent or bioactive compound,” as used herein, refers to acompound or entity that alters, inhibits, activates, or otherwiseaffects biological or chemical events. For example, bioactive agents mayinclude, but are not limited to, osteogenic or chondrogenic proteins orpeptides, anti-AIDS substances, anti-cancer substances, antibiotics,immunosuppressants, anti-viral substances, enzyme inhibitors, hormones,neurotoxins, opioids, hypnotics, anti-histamines, lubricants,tranquilizers, anti-convulsants, muscle relaxants and anti-Parkinsonsubstances, anti-spasmodics and muscle contractants including channelblockers, miotics and anti-cholinergics, anti-glaucoma compounds,anti-parasite and/or anti-protozoal compounds, modulators ofcell-extracellular matrix interactions including cell growth inhibitorsand antiadhesion molecules, vasodilating agents, inhibitors of DNA, RNAor protein synthesis, anti-hypertensives, analgesics, anti-pyretics,steroidal and non-steroidal anti-inflammatory agents, anti-angiogenicfactors, angiogenic factors, anti-secretory factors, anticoagulantsand/or antithrombotic agents, local anesthetics, ophthalmics,prostaglandins, anti-depressants, anti-psychotic substances,anti-emetics, and imaging agents. In certain embodiments, the bioactiveagent is a drug. In some embodiments, the bioactive agent is a growthfactor, cytokine, extracellular matrix molecule or a fragment orderivative thereof, for example, a cell attachment sequence such as RGD.

“Biocompatible,” as used herein, refers to materials that, uponadministration in vivo, do not induce undesirable long-term effects.

“Bone,” as used herein, refers to bone that is cortical, cancellous orcortico-cancellous of autogenous, allogenic, xenogenic, or transgenicorigin.

“Demineralized,” as used herein, refers to any material generated byremoving mineral material from tissue, e.g., bone tissue. In certainembodiments, the demineralized compositions described herein includepreparations containing less than 5% calcium and preferably less than 1%calcium by weight. Partially demineralized bone (e.g., preparations withgreater than 5% calcium by weight but containing less than 100% of theoriginal starting amount of calcium) is also considered within the scopeof the disclosure. In some embodiments, demineralized bone has less than95% of its original mineral content. Demineralized is intended toencompass such expressions as “substantially demineralized,” “partiallydemineralized,” and “fully demineralized.”

“Demineralized bone matrix” or “DBM” as used herein, refers to anymaterial generated by removing mineral material from bone tissue. Insome embodiments, the DBM compositions as used herein includepreparations containing less than 5% calcium and preferably less than 1%calcium by weight. Partially demineralized bone (e.g., preparations withgreater than 5% calcium by weight but containing less than 100% of theoriginal starting amount of calcium) are also considered within thescope of the disclosure.

“Osteoconductive,” as used herein, refers to the ability of anon-osteoinductive substance to serve as a suitable template orsubstance along which bone may grow.

“Osteogenic,” as used herein, refers to the ability of an agent,material, or implant to enhance or accelerate the growth of new bonetissue by one or more mechanisms such as osteogenesis, osteoconduction,and/or osteoinduction.

“Osteoimplant,” as used herein, refers to any bone-derived implantprepared in accordance with the embodiments of this disclosure andtherefore is intended to include expressions such as bone membrane, bonegraft, etc.

“Osteoinductive,” as used herein, refers to the quality of being able torecruit cells from the host that have the potential to stimulate newbone formation. Any material that can induce the formation of ectopicbone in the soft tissue of an animal is considered osteoinductive.

“Superficially demineralized,” as used herein, refers to bone-derivedelements possessing at least about 90 weight percent of their originalinorganic mineral content, the expression “partially demineralized” asused herein refers to bone-derived elements possessing from about 8 toabout 90 weight percent of their original inorganic mineral content andthe expression “fully demineralized” as used herein refers to bonecontaining less than 8% of its original mineral context.

The term “allograft” refers to a graft of tissue obtained from a donorof the same species as, but with a different genetic make-up from, therecipient, as a tissue transplant between two humans.

The term “autologous” refers to being derived or transferred from thesame individual's body, such as for example an autologous bone marrowtransplant.

The term “morbidity” refers to the frequency of the appearance ofcomplications following a surgical procedure or other treatment.

The term “osteoinduction” refers to the ability to stimulate theproliferation and differentiation of pluripotent mesenchymal stem cells(MSCs). In endochondral bone formation, stem cells differentiate intochondroblasts and chondrocytes, laying down a cartilaginous ECM, whichsubsequently calcifies and is remodeled into lamellar bone. Inintramembranous bone formation, the stem cells differentiate directlyinto osteoblasts, which form bone through direct mechanisms.Osteoinduction can be stimulated by osteogenic growth factors, althoughsome ECM proteins can also drive progenitor cells toward the osteogenicphenotype.

The term “osteoconduction” refers to the ability to stimulate theattachment, migration, and distribution of vascular and osteogenic cellswithin the graft material. The physical characteristics that affect thegraft's osteoconductive activity include porosity, pore size, andthree-dimensional architecture. In addition, direct biochemicalinteractions between matrix proteins and cell surface receptors play amajor role in the host's response to the graft material.

The term “osteogenic” refers to the ability of a graft material toproduce bone independently. To have direct osteogenic activity, thegraft must contain cellular components that directly induce boneformation. For example, a collagen matrix seeded with activated MSCswould have the potential to induce bone formation directly, withoutrecruitment and activation of host MSC populations. Because manyosteoconductive scaffolds also have the ability to bind and deliverbioactive molecules, their osteoinductive potential will be greatlyenhanced.

The term “patient” refers to a biological system to which a treatmentcan be administered. A biological system can include, for example, anindividual cell, a set of cells (e.g., a cell culture), an organ, or atissue. Additionally, the term “patient” can refer to animals,including, without limitation, humans.

The term “treating” or “treatment” of a disease refers to executing aprotocol, which may include administering one or more drugs to a patient(human or otherwise), in an effort to alleviate signs or symptoms of thedisease. Alleviation can occur prior to signs or symptoms of the diseaseappearing, as well as after their appearance. Thus, “treating” or“treatment” includes “preventing” or “prevention” of disease. Inaddition, “treating” or “treatment” does not require completealleviation of signs or symptoms, does not require a cure, andspecifically includes protocols, which have only a marginal effect onthe patient.

The term “xenograft” refers to tissue or organs from an individual ofone species transplanted into or grafted onto an organism of anotherspecies, genus, or family.

DETAILED DESCRIPTION

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities of ingredients,percentages or proportions of materials, reaction conditions, and othernumerical values used in the specification and claims, are to beunderstood as being modified in all instances by the term “about.”Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the present disclosure. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques.

Certain terminology, which may be used in the following description isfor convenience only and is not limiting. For example, the words“right”, “left”, “top” and “bottom” designate directions in the drawingsto which reference is made. The words, “anterior”, “posterior”,“superior”, “inferior”, “lateral” and related words and/or phrasesdesignate preferred positions and orientations in the human body towhich reference is made and are not meant to be limiting. Theterminology includes the above-listed words, derivatives thereof andwords of similar import.

Bone allograft is a preferred material by surgeons for conductinginterbody fusions because it will remodel over time into host bonewithin the fusion mass, but a limitation with the allograft is that itis only available in limited size ranges making it difficult to provideinterbody implants in a preferred geometrical shape. On the other hand,synthetic polymers such as poly-ether-ether-ketone (PEEK) can bemanufactured into any geometrical shape, but have some strengthlimitations and are a permanent implant that will not remodel into hostbone over time like an allograft. Polymer compositions also do not allowfor direct bone attachment or bonding to further stabilize the implantand fusion mass.

The present disclosure overcomes the drawbacks by providing variousexemplary designs of bone implants comprising a composite of allografttissue and a non-bone material, such as a polymer (or other materialssuch as metal, ceramic or plastic). One exemplary configurationaccording to the present disclosure involves providing corticalallograft pieces that are mechanically interlocked together to form asingle interbody implant. A body, which comprises a non-bone material isprovided having cavities or inserts formed therein which are configuredto retain the allograft pieces. This composite design of the body and anallograft allows for the advantageous properties of each to be fullyrealized. According to one aspect, the body may be configured to retainas many allograft pieces as possible in order to optimize the surfacearea contact of the allograft with intervertebral endplates.

In some embodiments, the composite implant is configured to increase thesurface area contact of the allograft with the host bone, which willresult in faster fusion and incorporation of the composite implant intohost bone and ultimately a stronger fusion mass. In some embodiments,the allograft bone used in the implant is surface demineralization toincrease its osteoinductivity and fusion with the host bone. In someembodiments, the implant optimizes the non-bone and bone content of theimplant body such that the majority of the mechanical load is carried bythe allograft and the non-bone material's primary purpose is to hold theallograft pieces together.

In some embodiments, the portion of the allograft that is notdemineralized comprises load bearing and/or higher compressive strengthallograft material. Advantageously, it is noted that an implant devicemay be provided in any configuration, size and shape, as per therequirements of the desired target site. Thus, an almost unlimitedranges of sizes and shapes of optimized bone implant devices may beprovided. In one example, an implant device may be configured to beadapted for use as an interbody fusion device, e.g., in spinal fusionprocedures. However, alternate configurations of the implant device maybe contemplated to suit the needs of a patient's bone graft target site.

Radiographically, a fusion enabled with an implant device according tothe present disclosure will be easier to assess because of masking bythe solid material of the non-bone material. Such a composite designalso allows for more advanced insertion tools and interbody cagefeatures such as a cage inserter that rotates the implant towards thecenter of the disc as it is inserted. Such as feature is very difficultto incorporate into a pure allograft implant.

Another advantage is that an implant body according to the presentdisclosure can be inserted on its side and once in the disc spacerotated 90 degrees to jack open or distract open the disc space.

FIG. 1 is a top view of an exemplary composite bone implant device 100according to one embodiment. FIG. 2 is a front view of the device ofFIG. 1. Device 100 may be comprises a body 103 which may comprise, e.g.,a ‘skeleton’ structure configured to include at least one window orcavity 102, within which a substance 101, such as an allograft materialmay be inserted and retained. The term ‘cavity’ includes and encompassesvoids, apertures, bores, depressions, holes, indentations, grooves,channels, notches or the like. In some embodiments as shown, a pluralityof cavities 102 may be provided throughout one or more surfaces ofand/or within the body 103, thus enabling a plurality of allograftpieces to be retained by the body 103 in various locations.

The body 103 may comprise any non-bone composition, in particular, anybiocompatible material including but not limited to a metal, such as,for example, cobalt-chromium-molybdenum (CCM) alloys, titanium, titaniumalloys, stainless steel, aluminum, etc., a ceramic such as, for example,zirconium oxide, silicone nitride, etc., an allograft, an autograft, ametal-allograft composite, a polymer such as, for example, polyarylether ketone (PAEK), polyether ether ketone (PEEK), polyether ketoneketone (PEKK), polyetherketone (PEK), polyetherketoneether-ketone-ketone (PEK-EKK), etc. The polymers may be reinforced witha fiber such as, for example, a carbon fiber or other thin, stiff fiber.

Advantageously, the body 103 may be formed, e.g., via injection moldingand/or machining into any size or shape to accommodate the desiredapplication and/or delivery conditions. The body 103 may further beconfigured to include any desired features, such as cavities,projections, etc. in any desired location or orientation, as discussedfurther below.

The body 103 may also include a mechanism or feature for engaging animplant insertion instrument (shown in FIG. 10). The mechanism orfeature for engaging the insertion instrument may take on any formincluding, for example, one or more bores for receiving one or moreprojections (not shown) formed on the implant insertion instrument, oneor more projections (not shown) for engaging one or more bores (notshown) formed on the implant insertion instrument, one or more channels(not shown) for receiving one or more tips formed on the implantinsertion instrument, one or more threaded bores (not shown) forreceiving one or more threaded shafts or screws, etc.

The body 103 may also include a mechanism or features for reducingand/or preventing slippage or migration of the implant device 100 duringinsertion. For example, one or more surfaces of the body 103 may includeprojections such as ridges or teeth (not shown) for increasing thefriction between the device 100 and the adjacent contacting surfaces ofthe vertebral bodies so to prevent movement of the implant device 100after introduction to a desired disc space.

In some embodiments, the surfaces of the body 103 include at least onecavity 102 or a plurality of cavities 102. Each cavity 102 may beprovided in any of a variety of shapes in addition to the generallyrectangular shape shown, e.g., in FIGS. 1 and 2, including but notlimited to generally circular, oblong, curved, triangular and otherpolygonal or non-polygonal shapes. The same or different types of cavityshapes and sizes may be provided in each body 103. Each cavity 102 maybe formed to pass entirely through the body 103 for promoting fusionbetween the upper and lower vertebral bodies so as to allow a boneybridge to form through the implant device 100. Alternately, cavities 102may be formed to partially pass through the body 103, or may be formedonly on one or more surfaces thereof.

In addition to the body 103 being enabled to be provided in variousconfigurations, shapes and sizes, the body 103 may include any number ofcavities 102 in different arrangements, locations, sizes and shapes. Forexample, the arrangement and location of cavities 102 may be determinedbased on application of the implant device 100. Alternate embodimentsshowing non-limiting examples of the various arrangements of cavities102 are shown in FIGS. 3-9 and discussed further below.

According to some embodiments, fusion may be facilitated or augmented byintroducing or positioning various osteoinductive materials within thecavities in the implant device. Such osteoinductive materials may beintroduced before, during, or after insertion of the exemplary implantdevice, and may include (but are not necessarily limited to) autologousbone harvested from the patient receiving the implant device, boneallograft, bone xenograft, any number of non-bone implants (e.g.ceramic, metallic, polymer), bone morphogenic protein, and/orbio-resorbable compositions.

FIGS. 3-4 are top views of exemplary composite interbody bone implantdevices 300, 400 for transforaminal lumbar interbody fusion (TLIF)according to alternate embodiments. Devices for TLIF procedures may beformed in a generally crescent shape, as shown, to be best adapted tothe surgical site. Exemplary device 300 depicts two rectangular cavities102 in which a substance 101, such as an osteoinductive material, may beretained, while exemplary device 400 depicts a center oval cavity 102and two adjacent circular cavities 104 in which a substance 101, such asan osteoinductive material, may be retained.

FIGS. 5, 7 and 8 are top views of exemplary composite interbody boneimplant devices for anterior lumbar interbody fusion (ALIF) according toalternate embodiments. FIG. 6 is a side view of the device of FIG. 5.Devices for ALIF procedures may be formed in a generally circular shape,preferably with a hole 105 formed in substantially a center thereof.Exemplary device 500 depicts three rectangular cavities arranged arounda hole 105. A substance 101, such as an osteoinductive material, may beretained in the cavities. Exemplary device 700 depicts two curvedcrescent-shaped cavities arranged around a hole 105. A substance 101,such as an osteoinductive material, may be retained in the cavities 102.Exemplary device 800 depicts four oval cavities 102 arranged around ahole 105, wherein a substance such as an osteoinductive material 101 maybe retained within the cavities 102. The body 103 of the device is shownin FIGS. 1-12.

In some embodiments, the implant device contacts host bone and theimplant device comprises non-bone material, the contact surface area ofthe non-bone material and the cortical bone to the host bone comprisesfrom about 5% to about 50% or from about 10% to about 20% of theimplant.

In some embodiments, the implant device comprises non-bone material andthe non-bone material comprises from about 10 wt. % to about 60 wt. % ofthe implant. In some embodiments, the implant device comprises bonematerial and the bone material comprises from about 10 wt. % to about 60wt. % of the implant.

In some embodiments, the bone allograft material comprises demineralizedbone matrix fibers and demineralized bone matrix chips in a ratio of25:75 to about 75:25 fibers to chips.

In some embodiments, the device comprises a plurality of cavities whereall or some of the plurality of cavities are empty and configured toreceive bone graft material, autograft bone material, ceramic bone voidfillers, demineralized bone matrix, or one or more growth factors. Thecavities can be partially or completely filled before the device isimplanted. The filling can occur in, for example, the operating roombefore the device is implanted into the subject.

In some embodiments, the composite interbody bone implant may comprisean allograft portion that is configured to be joined to anotherallograft portion or a non-allograft portion comprising a polymer. Inthis way, the composite interbody device can be joined before it isimplanted at or neat the target site. The composite interbody implantcan have mating surfaces comprising recesses and/or projections andreciprocating recesses and/or projections (e.g., joints) that allow theimplant to be assembled before implantation. Assembly can also include,for example, use of an adhesive material to join parts of the implanttogether and provide strong interlocking fit.

The adhesive material may comprise polymers having hydroxyl, carboxyl,and/or amine groups. In some embodiments, polymers having hydroxylgroups include synthetic polysaccharides, such as for example, cellulosederivatives, such as cellulose ethers (e.g., hydroxypropylcellulose). Insome embodiments, the synthetic polymers having a carboxyl group, maycomprise poly(acrylic acid), poly(methacrylic acid), poly(vinylpyrrolidone acrylic acid-N-hydroxysuccinimide), and poly(vinylpyrrolidone-acrylic acid-acrylic acid-N-hydroxysuccinimide)terpolymer.For example, poly(acrylic acid) with a molecular weight greater than250,000 or 500,000 may exhibit particularly good adhesive performance.In some embodiments, the adhesive can be a polymer having a molecularweight of about 2,000 to about 5,000, or about 10,000 to about 20,000 orabout 30,000 to about 40,000.

In some embodiments, the adhesive can comprise imido ester,p-nitrophenyl carbonate, N-hydroxysuccinimide ester, epoxide,isocyanate, acrylate, vinyl sulfone, orthopyridyl-disulfide, maleimide,aldehyde, iodoacetamide or a combination thereof. In some embodiments,the adhesive material can comprise at least one of fibrin, acyanoacrylate (e.g., N-butyl-2-cyanoacrylate, 2-octyl-cyanoacrylate,etc.), a collagen-based component, a glutaraldehyde glue, a hydrogel,gelatin, an albumin solder, and/or a chitosan adhesives. In someembodiments, the hydrogel comprises acetoacetate esters crosslinked withamino groups or polyethers as mentioned in U.S. Pat. No. 4,708,821. Insome embodiments, the adhesive material can comprise poly(hydroxylic)compounds derivatized with acetoacetate groups and/or polyaminocompounds derivatized with acetoacetamide groups by themselves or thecombination of these compounds crosslinked with an amino-functionalcrosslinking compounds.

The adhesive can be a solvent based adhesive, a polymer dispersionadhesive, a contact adhesive, a pressure sensitive adhesive, a reactiveadhesive, such as for example multi-part adhesives, one part adhesives,heat curing adhesives, moisture curing adhesives, or a combinationthereof or the like. The adhesive can be natural or synthetic or acombination thereof.

Contact adhesives are used in strong bonds with high shear-resistance.Pressure sensitive adhesives form a bond by the application of lightpressure to bind the adhesive with the target tissue site, cannulaand/or expandable member. In some embodiments, to have the device adhereto the target tissue site, pressure is applied in a directionsubstantially perpendicular to a surgical incision.

Multi-component adhesives harden by mixing two or more components, whichchemically react. This reaction causes polymers to cross-link intoacrylics, urethanes, and/or epoxies. There are several commercialcombinations of multi-component adhesives in use in industry. Some ofthese combinations are: polyester resin-polyurethane resin;polyols-polyurethane resin, acrylic polymers-polyurethane resins or thelike. The multi-component resins can be either solvent-based orsolvent-less. In some embodiments, the solvents present in the adhesivesare a medium for the polyester or the polyurethane resin. Then thesolvent is dried during the curing process.

In some embodiments, the adhesive can be a one-part adhesive. One-partadhesives harden via a chemical reaction with an external energy source,such as radiation, heat, and moisture. Ultraviolet (UV) light curingadhesives, also known as light curing materials (LCM), have becomepopular within the manufacturing sector due to their rapid curing timeand strong bond strength. Light curing adhesives are generally acrylicbased. The adhesive can be a heat-curing adhesive, where when heat isapplied (e.g., body heat), the components react and cross-link. Thistype of adhesive includes epoxies, urethanes, and/or polyimides. Theadhesive can be a moisture curing adhesive that cures when it reactswith moisture present (e.g., bodily fluid) on the substrate surface orin the air. This type of adhesive includes cyanoacrylates or urethanes.The adhesive can have natural components, such as for example, vegetablematter, starch (dextrin), natural resins or from animals e.g. casein oranimal glue. The adhesive can have synthetic components based onelastomers, thermoplastics, emulsions, and/or thermosets includingepoxy, polyurethane, cyanoacrylate, or acrylic polymers.

In some embodiments, the interbody bone implant may be joined togetherutilizing pins, rods, clips, or other fasteners to allow strong andeasily coupling of component parts. In some embodiments, the allograftmaterial is configured to provide the most contact to tissue surfaces(e.g., the allograft material can be on the perimeter of the device,while the polymer material is situated in the interior of the device.

FIG. 9 is a top view of an exemplary composite interbody bone implantdevice for anterior cervical discectomy and fusion (ACDF) according toan alternate embodiment. Devices for ACDF procedures may be formed in ageneral D-shape, preferably with a hole 105 formed substantially in acenter thereof. Exemplary device 900 depicts four circular cavities 102arranged around a hole 105, and a rectangular cavity opposed to the fourholes. A substance such as a biocompatible material may be inserted andretained within the cavities 102. The biocompatible material maycomprise, e.g., an osteoinductive material 101.

In one embodiment, the osteoinductive material comprises allografttissue. Non-limiting examples of a bone graft material includedemineralized bone matrix, or a bone composite. While allograft bone isa desirable alternative to autograft, it must be rigorously processedand terminally sterilized prior to implantation to remove the risk ofdisease transmission or an immunological response. This processingremoves the osteogenic and osteoinductive properties of the allograft,leaving only an osteoconductive scaffold. These scaffolds are availablein a range of preparations (such as morselized particles and struts) fordifferent orthopedic applications.

In one embodiment, to improve the osteoinductive properties, it isdesirable to use demineralized bone matrix (DBM) as the osteoinductivematerial, due to its superior biological properties relative toundemineralised allograft bone, since the removal of minerals increasesthe osteoinductivity of the graft. Currently, there are a range of DBMproducts in clinical use.

Demineralized bone matrix (DBM) is demineralized allograft bone withosteoinductive activity. DBM is prepared by acid extraction of allograftbone, resulting in loss of most of the mineralized component butretention of collagen and noncollagenous proteins, including growthfactors. DBM does not contain osteoprogenitor cells, but the efficacy ofa demineralized bone matrix as a bone-graft substitute or extender maybe influenced by a number of factors, including the sterilizationprocess, the carrier, the total amount of bone morphogenetic protein(BMP) present, and the ratios of the different BMPs present. DBMincludes demineralized pieces of cortical bone to expose theosteoinductive proteins contained in the matrix. These activateddemineralized bone particles are usually added to a substrate or carrier(e.g. glycerol or a polymer). DBM is mostly an osteoinductive product,but lacks enough induction to be used on its own in challenging healingenvironments such as posterolateral spine fusion.

According to some embodiments of the disclosure, the demineralized bonematrix may comprise demineralized bone matrix fibers and/ordemineralized bone matrix chips. In some embodiments, the demineralizedbone matrix may comprise demineralized bone matrix fibers anddemineralized bone matrix chips in a 30:60 ratio.

According to one embodiment of the disclosure, the bone compositecomprises a bone powder, a polymer and a demineralized bone. Indifferent embodiments of the disclosure, bone powder content can rangefrom about 5% to about 90% w/w, polymer content can range from about 5%to about 90% w/w, and demineralized bone particles content comprises thereminder of the composition. Preferably, the demineralized boneparticles comprise from about 20% to about 40% w/w while the polymer andthe bone powder comprise each from about 20% to about 60% w/w of thecomposition. The bone graft materials of the present disclosure includethose structures that have been modified in such a way that the originalchemical forces naturally present have been altered to attract and bindmolecules, including, without limitation, growth factors and/or cells,including cultured cells.

Namely, the demineralized allograft bone material may be furthermodified such that the original chemical forces naturally present havebeen altered to attract and bind growth factors, other proteins andcells affecting osteogenesis, osteoconduction and osteoinduction. Forexample, a demineralized allograft bone material may be modified toprovide an ionic gradient to produce a modified demineralized allograftbone material, such that implanting the modified demineralized allograftbone material results in enhanced ingrowth of host bone.

In one embodiment an ionic force change agent may be applied to modifythe demineralized allograft bone material. The demineralized allograftbone material may comprise, e.g., a demineralized bone matrix (DBM)comprising fibers, particles and any combination of thereof. Accordingto another embodiment, a bone graft structure may be used whichcomprises a composite bone, which includes a bone powder, a polymer anda demineralized bone.

The ionic force change agent may be applied to the entire demineralizedallograft bone material or to selected portions/surfaces thereof.

The ionic force change agent may be a binding agent, which modifies thedemineralized allograft bone material or bone graft structure to bindmolecules, such as, for example, growth factors, or cells, such as, forexample, cultured cells, or a combination of molecules and cells. In thepractice of the disclosure the growth factors include but are notlimited to BMP-2, rhBMP-2, BMP-4, rhBMP-4, BMP-6, rhBMP-6, BMP-7(OP-1),rhBMP-7, GDF-5, LIM mineralization protein, platelet derived growthfactor (PDGF), transforming growth factor-β(TGF-β), insulin-relatedgrowth factor-I (IGF-I), insulin-related growth factor-II (IGF-II),fibroblast growth factor (FGF), beta-2-microglobulin (BDGF II), andrhGDF-5. A person of ordinary skill in the art will appreciate that thedisclosure is not limited to growth factors only. Other molecules canalso be employed in the disclosure. For example, tartrate-resistant acidphosphatase, which is not a growth factor, may also be used in thedisclosure.

If a cell culture is employed, the cells include but are not limited tomesenchymal stems cells, pluripotent stem cells, osteoprogenitor cells,osteoblasts, osteoclasts, and any bone marrow-derived cell lines.

In some embodiments, the ionic force change agent comprises at least oneof enzymes, enzyme mixtures, pressure (e.g., isostatic pressure),chemicals, heat, sheer force, oxygen plasma, or a combination thereof.For example, the ionic force change agent may comprise an enzyme such ascollagenase or pepsin, which can be administered for a sufficient periodof time to partially digest at least a portion of the demineralizedallograft bone material. Subsequently, the enzyme may be deactivatedand/or removed.

Any enzyme or enzyme mixture may be contemplated, and treatment timedurations may be altered in accordance with the enzyme(s) used. Somesuitable enzymes that may degrade the DBM material include, but are notlimited to, cysteine proteinases, matrix metalloproteinases, enzymessuch as amylases, proteases, lipases, pectinases, cellulases,hemicellulases, pentosanases, xylanases, phytases or combinationsthereof. Exemplary enzymes suitable to partially degrade and modify theDBM material, include but are not limited to, cathepsin L, cathepsin K,cathepsin B, collagenase, pepsin, plasminogen, elastase, stromelysin,plasminogen activators, or a combination thereof.

In some embodiments, the DBM material can be subjected to pressure tomodify it. The simplest pressing technique is to apply pressure to theunconstrained DBM material. Examples include pressing the DBM materialusing a mortar and pestle, applying a rolling/pressing motion such as isgenerated by a rolling pin, or pressing the bone pieces between flat orcurved plates. These flattening pressures cause the DBM material fibersto remain intact.

Another pressing technique involves mechanically pressing demineralizedbone material, which can be constrained within a sealed chamber having ahole (or a small number of holes) in its floor or bottom plate. Theseparated fibers extrude through the holes with the hole diameterlimiting the maximum diameter of the extruded fibers. This constrainedtechnique results in fibers that are largely intact (as far as length isconcerned).

In a combined unconstrained/constrained pressing technique that resultsin longer fibers by minimizing fiber breakage, the demineralized bone isfirst pressed into an initially separated mass of fibers while in theunconstrained condition and thereafter these fibers are constrainedwithin the sealed chamber where pressing is continued.

In general, pressing of demineralized bone to provide demineralized boneparticles can be carried out at from about 1,000 to about 40,000 psi,and preferably at from about 5,000 to about 20,000 psi.

Subsequent to the addition of the ionic force change agent, thepractitioner may optionally administer an appropriate molecule or cellculture. Generally, the molecule or cell culture is applied withinminutes, for example from about 1 to about 120 minutes beforeimplantation into the patient.

One class of molecules suitable for one embodiment of the disclosure isgrowth factors. Growth factors suitable for use in the practice of thedisclosure include but are not limited to bone morphogenic proteins, forexample, BMP-2, rhBMP-2, BMP-4, rhBMP-4, BMP-6, rhBMP-6, BMP-7 (OP-1),rhBMP-7, GDF-5, and rhGDF-5. Bone morphogenic proteins have been shownto be excellent at growing bone and there are several products beingtested. For example, rhBMP-2 delivered on an absorbable collagen sponge(INFUSE® Bone Graft, Medtronic Sofamor Danek, Memphis, Tenn.) has beenused inside titanium fusion cages and resulted in successful fusion andcan be used on a ceramic carrier to enhance bone growth in aposterolateral fusion procedure. rhBMP-2 can also be used on a carrierfor acute, open fractures of the tibial shaft. BMP-7 (OP-1) alsoenhances bone growth in a posterolateral fusion procedure.

Additionally, suitable growth factors include, without limitation, LIMmineralization protein, platelet derived growth factor (PDGF),transforming growth factor β (TGF-β), insulin-related growth factor-I(IGF-I), insulin-related growth factor-II (IGF-II), fibroblast growthfactor (FGF), and beta-2-microglobulin (BDGF II).

Further, molecules, which do not have growth factor properties may alsobe suitable for this disclosure. An example of such molecules istartrate-resistant acid phosphatase.

In one embodiment, the demineralized allograft bone material is treatedwith a negatively-charged ionic force change agent to produce anegatively-charged demineralized allograft bone material. Thenegatively-charged demineralized allograft bone material attracts apositively charged molecule having a pI from about 8 to about 10.Examples of positively charged molecules having a pI from about 8 toabout 10 include but are not limited to, rhBMP-2 and rhBMP-6.

In another embodiment, the demineralized allograft bone material istreated with a positively-charged ionic force change agent such that thepositively-charged demineralized allograft bone material attracts amolecule with a slightly negative charge, for example a charge of pIabout 5 to about 7. Examples of molecules having a slightly negativecharge include rhBMP-4.

In yet another embodiment, the demineralized allograft bone material istreated with a positively-charged ionic force change agent to produce apositively-charged demineralized allograft bone material such thatcells, in particular cell cultures having a negative surface charge bindto the positively-charged demineralized allograft bone material.Examples of cells which are suitable for use in the practice of thedisclosure include but are not limited to mesenchymal stems cells,pluripotent stem cells, embryonic stem cells, osteoprogenitor cells andosteoblasts.

The mechanisms by which a demineralized allograft bone material mayacquire ionic forces include but are not limited to ionization, ionadsorption and ion dissolution.

In one embodiment, the implant is modified to give it the selectedcharge by a one-to-one substitution of the calcium ion with lithium,sodium, potassium or cesium of hydroxyapatite.

In yet another aspect, treatments with gradient-affecting elements, suchas elements present in hydroxyapatite, and human proteins are employed.Suitable gradient-affecting proteins are those present in the organicphase of human bone tissue. The gradient-affecting proteins derivemolecule or cell attraction without the potential damaging effects onthe implants, as may be the case with other chemical treatments. Usuallythis is accomplished through surface treatments such as, for example,plasma treatment to apply an electrostatic charge on bone.

The term “plasma” in this context is an ionized gas containing excitedspecies such as ions, radicals, electrons and photons. The term “plasmatreatment” refers to a protocol in which a surface is modified using aplasma generated from process gases including, but not limited to, O₂,He, N₂, Ar and N₂O. To excite the plasma, energy is applied to thesystem through electrodes. This power may be alternating current (AC),direct current (DC), radiofrequency (RF), or microwave frequency (MW).The plasma may be generated in a vacuum or at atmospheric pressure. Theplasma can also be used to deposit polymeric, ceramic or metallic thinfilms onto surfaces. Plasma treatment is an effective method touniformly alter the surface properties of substrates having different orunique size, shape and geometry including but not limited to bone andbone composite materials.

In some embodiments, the implant device 100 of the present disclosurehaving osteoinductive material retained therein may be used to providetemporary or permanent fixation along an orthopedic target site. Forexample, the implant device 100 may be introduced into an intervertebraldisc space while secured to a surgical insertion instrument andthereafter manipulated into the proper orientation before beingreleased. According to one aspect, the implant device 100 may beintroduced into a target site through use of any of a variety ofsuitable surgical instruments having the capability to engage theimplant device 100. For example, a clinician may utilize the implant 100in a minimally invasive spinal fusion procedure. After creation of aworking channel and preparation of the disc space, a single implantdevice 100 may be grasped and placed into the intervertebral disc space.Additional materials and tools may be included in the procedure before,during, or after the insertion of the implant 10 to aid in introducingthe implant into a targeted spinal site.

FIG. 10 is an exemplary depiction of an implant device 1001 grasped byan insertion tool 201. The tool 201 may be adapted to be affixed to theparticular dimensions of the implant device 1001 for secure andeffective manipulation of the device during implantation procedures.Advantageously, the tool 201 may enable rotation of the implant device1001 within an intervertebral space after insertion therein. The devicecan have a substance disposed in any one of the cavities.

FIG. 11 depicts side and top views of an exemplary implant deviceinserted within an intervertebral disc space 203 in a first position.FIG. 12 depicts side and top views of an exemplary implant deviceinserted within an intervertebral disc space 203 and rotated to a secondposition, which causes the disc space 203 to be increased.

To facilitate rotation and effective distraction, an implant deviceaccording to the present disclosure may be formed having a shape anddimensions to provide, e.g., a desired amount of self-distraction of thedisc space during insertion of the implant device. For example, in someembodiments as shown in FIGS. 11 and 12, an implant device is providedwhich is formed to have a thickness 201 which is less than at least oneof its length 207 and width 205. Initially, the implant device may beinserted to have its thickness 201 placed within the disc space 203. Theimplant device, being advantageously configured to be effectivelygrasped by a surgical instrument, may then be rotated (e.g., 90 degreesin either direction) to effectively jack open or distract open the discspace by causing the increased dimensions of either the length or widthto be placed between the disc space 203. The device can have a substance101 disposed in the cavity of uniformly throughout the body 103 or atdiscrete positions in the cavity or body 103.

Having been deposited in the disc space, an implant device of thepresent disclosure effects spinal fusion over time as the naturalhealing process integrates and binds the implant within theintervertebral space by allowing a boney bridge to form through theimplant and between the adjacent vertebral bodies.

In some embodiments, an implant device of the present disclosure may beused to deliver substances such as surface demineralized bone chips,optionally of a predetermined particle size, demineralized bone fibers,optionally pressed, and/or allograft.

For embodiments where the substance is biologic, the substance may beautogenic, allogenic, xenogenic, or transgenic. However, it iscontemplated that other suitable materials may be positioned in theimplant device such as, for example, protein, nucleic acid,carbohydrate, lipids, collagen, allograft bone, autograft bone,cartilage stimulating substances, allograft cartilage, TCP,hydroxyapatite, calcium sulfate, polymer, nanofibrous polymers, growthfactors, carriers for growth factors, growth factor extracts of tissues,demineralized bone matrix, dentine, bone marrow aspirate, bone marrowaspirate combined with various osteoinductive or osteoconductivecarriers, concentrates of lipid derived or marrow derived adult stemcells, umbilical cord derived stem cells, adult or embryonic stem cellscombined with various osteoinductive or osteoconductive carriers,transfected cell lines, bone forming cells derived from periosteum,combinations of bone stimulating and cartilage stimulating materials,committed or partially committed cells from the osteogenic orchondrogenic lineage, or combinations of any of the above. In someembodiments, the substance may be pressed before placement in theimplant device. A substance provided within the implant device may behomogenous, or generally a single substance, or may be heterogeneous, ora mixture of substances.

In some embodiments, the substance may be designed to expand in vivo.Such an embodiment may be used to fill a space and create contact withcongruent surfaces as it expands in vivo, for example for interbodyfusion. Thus, in some embodiments, the implant device may be used in thedisc space, between implants, or inside a cage.

In some embodiments the substance delivered by the implant device mayinclude or comprise an additive such as an angiogenesis promotingmaterial or a bioactive agent. It will be appreciated that the amount ofadditive used may vary depending upon the type of additive, the specificactivity of the particular additive preparation employed, and theintended use of the composition. The desired amount is readilydeterminable by one skilled in the art. Angiogenesis may be an importantcontributing factor for the replacement of new bone and cartilagetissues. In certain embodiments, angiogenesis is promoted so that bloodvessels are formed at an implant site to allow efficient transport ofoxygen and other nutrients and growth factors to the developing bone orcartilage tissue. Thus, angiogenesis promoting factors may be added tothe substance to increase angiogenesis. For example, class 3semaphorins, e.g., SEMA3, controls vascular morphogenesis by inhibitingintegrin function in the vascular system, and may be included in therecovered hydroxyapatite.

In accordance with some embodiments, the substance may be supplemented,further treated, or chemically modified with one or more bioactiveagents or bioactive compounds. Bioactive agent or bioactive compound, asused herein, refers to a compound or entity that alters, inhibits,activates, or otherwise affects biological or chemical events. Forexample, bioactive agents may include, but are not limited to,osteogenic or chondrogenic proteins or peptides; demineralized bonepowder; collagen, insoluble collagen derivatives, etc., and solublesolids and/or liquids dissolved therein; anti-AIDS substances;anti-cancer substances; antimicrobials and/or antibiotics such aserythromycin, bacitracin, neomycin, penicillin, polymycin B,tetracyclines, biomycin, chloromycetin, and streptomycins, cefazolin,ampicillin, azactam, tobramycin, clindamycin and gentamycin, etc.;immunosuppressants; anti-viral substances such as substances effectiveagainst hepatitis; enzyme inhibitors; hormones; neurotoxins; opioids;hypnotics; anti-histamines; lubricants; tranquilizers; anti-convulsants;muscle relaxants and anti-Parkinson substances; anti-spasmodics andmuscle contractants including channel blockers; miotics andanti-cholinergics; anti-glaucoma compounds; anti-parasite and/oranti-protozoal compounds; modulators of cell-extracellular matrixinteractions including cell growth inhibitors and antiadhesionmolecules; vasodilating agents; inhibitors of DNA, RNA, or proteinsynthesis; anti-hypertensives; analgesics; anti-pyretics; steroidal andnon-steroidal anti-inflammatory agents; anti-angiogenic factors;angiogenic factors and polymeric carriers containing such factors;anti-secretory factors; anticoagulants and/or antithrombotic agents;local anesthetics; ophthalmics; prostaglandins; anti-depressants;anti-psychotic substances; anti-emetics; imaging agents;biocidal/biostatic sugars such as dextran, glucose, etc.; amino acids;peptides; vitamins; inorganic elements; co-factors for proteinsynthesis; endocrine tissue or tissue fragments; synthesizers; enzymessuch as alkaline phosphatase, collagenase, peptidases, oxidases, etc.;polymer cell scaffolds with parenchymal cells; collagen lattices;antigenic agents; cytoskeletal agents; cartilage fragments; living cellssuch as chondrocytes, bone marrow cells, mesenchymal stem cells; naturalextracts; genetically engineered living cells or otherwise modifiedliving cells; expanded or cultured cells; DNA delivered by plasmid,viral vectors, or other means; tissue transplants; autogenous tissuessuch as blood, serum, soft tissue, bone marrow, etc.; bioadhesives; bonemorphogenic proteins (BMPs); osteoinductive factor (IFO); fibronectin(FN); endothelial cell growth factor (ECGF); vascular endothelial growthfactor (VEGF); cementum attachment extracts (CAE); ketanserin; humangrowth hormone (HGH); animal growth hormones; epidermal growth factor(EGF); interleukins, e.g., interleukin-1 (IL-1), interleukin-2 (IL-2);human alpha thrombin; transforming growth factor (TGF-β); insulin-likegrowth factors (IGF-1, IGF-2); parathyroid hormone (PTH); plateletderived growth factors (PDGF); fibroblast growth factors (FGF, BFGF,etc.); periodontal ligament chemotactic factor (PDLGF); enamel matrixproteins; growth and differentiation factors (GDF); hedgehog family ofproteins; protein receptor molecules; small peptides derived from growthfactors above; bone promoters; cytokines; somatotropin; bone digesters;antitumor agents; cellular attractants and attachment agents;immuno-suppressants; permeation enhancers, e.g., fatty acid esters suchas laureate, myristate and stearate monoesters of polyethylene glycol,enamine derivatives, alpha-keto aldehydes, etc.; and nucleic acids.

In certain embodiments, the bioactive agent may be a drug. In someembodiments, the bioactive agent may be a growth factor, cytokine,extracellular matrix molecule, or a fragment or derivative thereof, forexample, a protein or peptide sequence such as RGD.

In one embodiment of an implant device comprising at least one cavity,it may be contemplated that any combination or mixture of same ordifferent substances may be placed and retained therein, and further,different substances may be placed within the same or differentcavities.

Sterilization

A medical implant device according to the present disclosure includingits contents may be sterilizable. In various embodiments, one or morecomponents of the implant device and/or its contents are sterilized byradiation in a terminal sterilization step in the final packaging.Terminal sterilization of a product provides greater assurance ofsterility than from processes such as an aseptic process, which requireindividual product components to be sterilized separately and the finalpackage assembled in a sterile environment.

In various embodiments, gamma radiation is used in the terminalsterilization step, which involves utilizing ionizing energy from gammarays that penetrates deeply in the device. Gamma rays are highlyeffective in killing microorganisms, they leave no residues nor havesufficient energy to impart radioactivity to the device. Gamma rays canbe employed when the device is in the package and gamma sterilizationdoes not require high pressures or vacuum conditions, thus, packageseals and other components are not stressed. In addition, gammaradiation eliminates the need for permeable packaging materials.

In various embodiments, electron beam (e-beam) radiation may be used tosterilize one or more components of the device. E-beam radiationcomprises a form of ionizing energy, which is generally characterized bylow penetration and high-dose rates. E-beam irradiation is similar togamma processing in that it alters various chemical and molecular bondson contact, including the reproductive cells of microorganisms. Beamsproduced for e-beam sterilization are concentrated, highly-chargedstreams of electrons generated by the acceleration and conversion ofelectricity. E-beam sterilization may be used, for example, when themedical device has gel components.

Other methods may also be used to sterilize the device and/or one ormore components of the device and/or contents, including, but notlimited to, gas sterilization, such as, for example, with ethylene oxideor steam sterilization.

Method of Use

An implant device according to the present disclosure delivers thesubstance or substances in vivo. Active delivery of the substance mayinclude the cleavage of physical and/or chemical interactions ofsubstance from covering with the presence of body fluids, extracellularmatrix molecules, enzymes or cells. Further, it may comprise formationchange of substances (growth factors, proteins, polypeptides) by bodyfluids, extracellular matrix molecules, enzymes or cells.

The body of the implant device is loaded with the substance forplacement in vivo. The body may be pre-loaded, thus loaded atmanufacture, or may be loaded in the operating room or at the surgicalsite. Preloading may be done with any of the substances previouslydiscussed including, for example, allograft such as DBM, syntheticcalcium phosphates, synthetic calcium sulfates, enhanced DBM, collagen,carrier for stem cells, and expanded cells (stem cells or transgeniccells). Loading in the operating room or at the surgical site may bedone with any of these materials and further with autograft and/or bonemarrow aspirate.

Any suitable method may be used for loading a substance in the implantdevice in the operating room or at the surgical site. For example, thesubstance may be spooned into the cavity(ies) of the implant device, thesubstance may be placed in the implant device using forceps, thesubstance may be loaded into the implant device using a syringe (with orwithout a needle), or the substance may be inserted into the implantdevice in any other suitable manner. Specific embodiments for loading atthe surgical site include for example, vertebroplasty or interbody spacefiller.

For placement, the substance or substances may be provided in theimplant device and the implant device placed in vivo. In one embodiment,the implant device is placed in vivo by placing the implant device in acatheter or tubular inserter and delivering the implant device with thecatheter or tubular inserter. The implant device, with a substanceprovided therein, may be steerable such that it can be used withflexible introducer instruments for, for example, minimally invasivespinal procedures. For example, the implant device may be introduceddown a tubular retractor or scope, during XLIF, TLIF, or otherprocedures. In other embodiments, the implant device (with or withoutsubstance loaded) may be placed in a cage, for example, for interbodyfusion.

Attachment mechanisms provided on the implant device may be used tocouple the device to a site in vivo.

Applications

An implant device according to the present disclosure may be configuredfor use in any suitable application. In some embodiments, the implantdevice may be used in healing vertebral compression fractures, interbodyfusion, minimally invasive procedures, posterolateral fusion, correctionof adult or pediatric scoliosis, treating long bone defects,osteochondral defects, ridge augmentation (dental/craniomaxillofacial,e.g. edentulous patients), beneath trauma plates, tibial plateaudefects, filling bone cysts, wound healing, around trauma, contouring(cosmetic/plastic/reconstructive surgery), and others. The implantdevice may be used in a minimally invasive procedure via placementthrough a small incision, via delivery through a tube, or other. Thesize and shape of the device may advantageously be designed inaccordance with restrictions on delivery conditions.

An exemplary application for using an implant device as disclosed isfusion of the spine. In clinical use, the implant device and deliveredsubstance may be used to bridge the gap between the transverse processesof adjacent or sequential vertebral bodies. The implant device may beused to bridge two or more spinal motion segments. The implant devicesurrounds the substance to be implanted, and contains the substance toprovide a focus for healing activity in the body.

In other applications, the implant device may be applied to transverseprocesses or spinous processes of vertebrae.

Generally, the implant device may be applied to a pre-existing defect,to a created channel, or to a modified defect. Thus, for example, achannel may be formed in a bone, or a pre-existing defect may be cut toform a channel, for receipt of the implant device. The implant devicemay be configured to match the channel or defect. In some embodiments,the configuration of the implant device may be chosen to match thechannel. In other embodiments, the channel may be created, or the defectexpanded or altered, to reflect a configuration of the implant device.The implant device may be placed in the defect or channel and,optionally, coupled using attachment mechanisms.

At the time just prior to when the implant device is to be placed in adefect site, optional materials, e.g., autograft bone marrow aspirate,autograft bone, preparations of selected autograft cells, autograftcells containing genes encoding bone promoting action, etc., can becombined with the implant device and/or with a substance provided in theimplant device. The implant device can be implanted at the bone repairsite, if desired, using any suitable affixation means, e.g., sutures,staples, bioadhesives, screws, pins, rivets, other fasteners and thelike or it may be retained in place by the closing of the soft tissuesaround it.

Although the disclosure has been described with reference to someembodiments, persons skilled in the art will recognize that changes maybe made in form and detail without departing from the spirit and scopeof the disclosure.

What is claimed is:
 1. A bone implant device comprising: a monolithicbody, which comprises a non-bone composition formed into a shape andincluding at least one cavity, the composition comprising a polymercomprising poly-ether-ketone-ketone (PEKK), poly-ether-ether-ketone(PEEK), or a combination thereof; and a biocompatible material providedwithin the at least one cavity of the body, wherein the at least onecavity passes through the body, wherein the body is formable into ashape and size configured for implantation at a surgical site, whereinthe biocompatible material comprises demineralized bone matrix fibersand demineralized bone matrix chips in a 30:60 ratio, and thedemineralized bone matrix chips are surface demineralized and thedemineralized bone fibers are fully demineralized, wherein the devicecomprises a surface area and about 5% to about 50% or about 10% to about20% of the surface area is configured to contact host bone from anintervertebral endplate, wherein the biocompatible material comprisesallograft bone material and the allograft bone material comprises fromabout 10% to about 60% by weight of the device or from about 15% toabout 30% by weight of the device.
 2. A device of claim 1, wherein thenon-bone composition includes at least one of an additional polymer,ceramic, metal or combinations thereof.
 3. A device of claim 1, whereinthe body includes a plurality of cavities distributed throughoutsurfaces of the body.